The long range objective of this project is to elucidate the basic mechanisms of drug allergy in man, and to apply current and new knowledge to the development of diagnostic methods and therapeutic approaches to the clinical problems which drug hypersensitivity pose. The model system chosen for study is the most prevalent drug allergy, penicillin hypersensitivity. Our previous work supports the usefulness of skin testing with penicilloyl-polylysine and a minor determinant mixture of penicillin derivatives in predicting reactions to the drug. This finding suggests that reaginic (IgE) antibody plays a primary role in the pathogenesis of some allergic drug reactions. We have now developed an in vitro assay for penicilloyl-specific, IgE antibody employing the radioallergosorbent technique (RAST), and have begun to evaluate its predictive reliability as compared to direct skin testing. The in vitro RAST assay for IgE penicillin antibodies will be combined with a sensitive radioimmunoassay for IgG anti-penicillin antibody in a study of the immune response of man to penicillin administration. A study protocol will investigate the influence of immunological status, dose, route and duration of therapy, and physiological variables on the induction of anti-penicillin reagins.